development of an optically transparent silicon cmos technology platform for biological analysis
TRANSCRIPT
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Abstract— A prototype optical structure suitable for advanced
biological investigation has been successfully manufactured using
plasma enhanced chemical vapor deposition (PECVD) and deep
reactive ion etching (DRIE) techniques. Our approach to the
design and fabrication of the structure is such that it can easily be
integrated onto a lab-on-a-chip (LoC) cell positioning platform,
combining use of integrated circuit (IC) technology with optimal
in-situ analysis of cells through the substrate using high
resolution inverted microscope systems. This work describes the
concept, design, fabrication, and optical characterization of a
transparent window and corresponding via, which extends from
the top surface to bottom surface of a silicon wafer. The
effectiveness of the platform is demonstrated in multi-color
fluorescence imaging of cells, cultured on-chip, using an inverted,
confocal microscope.
Index Terms—CMOS, Dielectrophoresis (DEP), lab-on-a-chip
(LoC), on-chip imaging, on-chip microscopy. Manuscript received May 2nd , 2014
N. Davies is with SPTS, SPTS Technologies, Ringland Way, Newport, UK
NP18 2TA P. Holland, M. Holton, J. Wills, M. Rowan Brown and H.D. Summers are
with the College of Engineering, Swansea University, Swansea, UK SA2 8PP
* Corresponding author: [email protected] This work was funded by the UK’s Engineering and Physical Science
Research Council (EPSRC) First grant scheme; grant number EP/I038799/1
I. INTRODUCTION
dvances in the fabrication techniques of Complementary
Metal Oxide Semiconductor (CMOS) devices for
traditional electronic applications have enabled a new
technology to develop based on electrical and mechanical
operations. These devices termed Micro Electro Mechanical
Systems (MEMS) have evolved through continued
miniaturization to be used across a spectrum of application
areas. These advances have been adapted by and contributed
to ‘on-chip’ tools used in the biotechnology area and as a
consequence of these advancements; miniaturized and self
contained lab-on-a-chip (LoC) systems have been developed.
The traditional method of analyzing biological matter situated
on glass slides is through the use of inverted microscope [1].
Research effort to support effective single cell studies have
identified many techniques to physically manipulate cells [2],
some of which can be implemented on silicon, enabling access
to the power of the integrated circuit (IC). Indeed recent
innovations now allow the automated sorting and isolation of
single cells for biological investigation using LoC
technology[3, 4] and there is a need to integrate this additional
functionality within microscopy platforms. LoC silicon
technology utilizes the power of the integrated circuit to allow
high cell count sorting and positioning. A disadvantage of the
majority of the current generation of such devices is that when
the cell sorting procedure has been completed the isolated
cells then have to be removed to allow more detailed
biological analysis. If the isolated cells could be analyzed
without the need to be removed from the LoC device then the
process would not only gain advantages in terms of the speed
of the analysis but would also reduce the risk of cell damage
and contamination as the cells are moved to a different
medium. Recently some on chip imaging approaches have
emerged that use specific onboard optical biosensors and these
will be of particular use on point-of-care and field applications
[5-8]. However, these LoC onboard optic systems have not yet
reached the level of development of other detection methods
[9]. Whilst reasonable optical performance may be achieved
with integrated systems they can never match the ultimate in
resolution and sensitivity provided by high performance
microscopes. Thus the adaptation of silicon based LoC device
that could use optically transparent windows through the
structure of the integrated circuit in conjunction with modern
biotechnology analytical techniques, such as Epi-fluorescence
microscopy, would have advantages in cost, robustness and
accuracy. A fluorescence microscope is an example of a larger
more expensive piece of equipment that could be used in
conjunction with a cheaper LoC device that would give
consistent reliable results with a large throughput. This
method could also be expanded to include other optical
techniques such as differential interference contrast
microscopy, phase contrast microscopy, darkfield microscopy
and confocal microscopy [10-12].
Whilst silicon IC technology has been successfully
implemented to sort cells using dielectrophoresis [13], no
technology has previously been available to allow in-situ
optical analysis on inverted microscope systems. A concept to
achieve this aim is shown in Fig. 1. In our concept of a
transparent CMOS LoC the normal transistors forming mixed-
signal circuitry and passive components are fabricated in the
standard process. The dielectric layers of a CMOS device
isolate the conducting parts, such as the wire interconnects and
transistors, from one another and are typically made of silicon
based material. The electrical properties of these dielectric
layers such as breakdown voltage and leakage current are
essential to ensure that the CMOS device functions correctly.
Development of an Optically Transparent
Silicon Based Technology Platform for
Biological Analysis Nigel Davies, Huw D. Summers, Mark Holton, M. Rowan Brown, John Wills
and Paul Holland Member IEEE.
A
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Fig. 1. Schematic of the Proposed LoC CMOS Platform in Cross-Section.
The silicon materials used to fabricate these dielectric
layers also possess inherently good optical properties [14-16].
This leads to interesting possibilities for manipulation of the
refractive indices and thickness of these dielectric layers such
that the optical performance of the stack can be modified for
specific application requirements. For instance in the example
application shown in Fig. 1. the optical stack could be adjusted
to maximize the transmission of specific wavelengths used by
the fluorophores. However, the balance between optical and
electrical performance must be maintained if the functionality
of the CMOS platform is to be preserved.
In this paper we demonstrate the semiconductor fabrication
techniques required to form such an optical structure using
standard dielectric layers. Optical analysis of the dielectric
stacks is performed analytically using the Bayes-Spectral-
Entropy-Based measure of focus technique and is practically
demonstrated by imaging three color fluorescence lung
epithelial cells loaded with quantum dots. Physical optical
transmission measurements are used in conjunction with
computational modeling of transmission properties to
understand the observed thin film interference caused by the
multi-layer dielectric layer stack. The proposed structure is a
novel approach to the traditional method of optical sensing on
a LoC technology platform [17].
II. DEVICE FABRICATION
The CMOS architecture at the 0.35µm node suitable for
LoC work consists of at least three dielectric layers: the Pre-
Metal Dielectric (PMD), Inter-Metal Dielectric (IMD) and a
passivation layer [18]. The two test structures that were
fabricated are shown in Fig. 2. and are representative of a
CMOS device that has been designed with sufficient spacing
between the metal layers to allow the formation of the optical
structure. In this work, we use standard semiconductor
materials. Tetraethylorthosilicate (TEOS) is used to form the
PMD, TEOS to form the IMD of stack 1, Silicon Oxide
(SiO2) to form the IMD of stack 2 and Silicon Nitride (Si3N4)
to form the passivation layer [19-23].
Fig. 2. Schematic (a) Stack 1- TEOS-TEOS- Si3N4 (b) Stack 2 TEOS-SiO2-
Si3N4
725μm
Layer 1 (PMD) TEOS 2μm
Silicon Substrate Silicon Substrate
Etched Via
Layer 2 (IMD) TEOS 2μm
Layer 3 (Passivation) Si3N4 2μm
Layer 1 (PMD) TEOS 2μm
Silicon Substrate Silicon Substrate
Layer 2 (IMD) SiO2 2μm
Layer 3 (Passivation) Si3N4 2μm
Etched Via
1mm
725μm
1mm
(a)
1mm
(b)
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As different CMOS process architectures use different
planarization schemes, two different stacks were analyzed to
allow flexibility in future integration work. The utilization of
TEOS in the IMD layer of stack 1 would offer improved
planarization over the SiO2 IMD layer of stack 2. However,
TEOS is a more expensive option than SiO2 and should only
be used if required to achieve a specific CMOS architecture.
The dielectric layers were deposited using an SPTS
Technologies Advanced Plasma Module (APM®) that utilizes
Plasma Enhanced Chemical Vapor Deposition (PECVD)
technology.
The SiO2 films were deposited using a Gas flow regime of
1000sccm of N2, 2000sccm of N2O and 100sccm of SiH4,
Electrode Spacing of 20mm, High Frequency (HF) at
13.56MHz and 450W and a process pressure of 1500mTorr
[24]. The Si3N4 films used a Gas flow regime of 3600sccm of
N2, 950sccm of Ammonia and 400sccm of SiH4, Electrode
Spacing of 20mm, HF at 825W, Low Frequency (LF) at
375KHz and 400W and a process pressure of 2600mTorr
[25].The TEOS films used a Gas flow regime of 2700sccm of
O2, 500sccm of He used as a process stability gas and 2.5ccm
of liquid TEOS, Electrode Spacing of 12mm, HF at 1500W,
LF at 130W and a process pressure of 2700mTorr [26].
The difference between the stacks was that layer 2 (IMD) on
Stack 1 used TEOS and on Stack 2 used SiO2. Although
TEOS is more expensive it has improved planarization
properties and the use of TEOS for the IMD layer could be
necessary in some CMOS applications. The 300mm silicon
substrates used were 775μm thick. On completion of the
PECVD process the backside of the 300mm substrate was
masked which exposed different via areas ranging from
0.25mm2 to 2mm
2.
The etching of the silicon substrate through to the optical
structure was performed on a SPTS Technologies Rapier®
Deep Silicon Etch System. Many methods of silicon etching
exist therefore the correct process depends on the required
etch isotropy. It was assumed that a vertical anisotropic etch
would be required for this application so as to allow multiple
windows to be fabricated in close proximity. The reason why
plasma etching techniques were used was due to the fact that
chemical wet etching cannot achieve the anisotropic vertical
etch. However, it is only under certain dry etch process
conditions, referred to as the Bosch process, that a vertical
etch can be achieved [27, 28]. The Rapier module uses two
Radio Frequency (RF) sources which is unique for deep
reactive ion etching (DRIE) capital equipment and thus
benefits from the advantages of Inductive Coupled Plasma
(ICP) and a Deep Silicon Etch (DSE) bell jar source. The etch
process was performed using a variant of the Bosch process,
which consisted of cyclic C4F8 deposition and SF6 etch phases
at an etch pressure regime of 70mTorr. The wafer sat on an
Electrostatic Chuck on to which was applied 50W of HF
power at a temperature 10°C. The DSE source power was set
to 3.5kW of HF power and the ICP source power was set to
1.5kW of HF power. The etch depth was controlled by a
Claritas® endpoint system which optically monitored the
reactive species (etch by-products). In this case the reactive
species was Silicon Tetrafluoride (SiF4) at 440nm. The
substrate was then cleaved to expose the etched via and
dielectric stacks and examined on a Zeiss Supra 55VP
Scanning Electron Microscope (SEM), refer to Fig. 3.
(a)
(b)
(c)
Fig. 3. SEM images (a) Optical Structure (b) Stack 1- TEOS-TEOS- Si3N4 (c)
Stack 2 TEOS-SiO2- Si3N4
III. ELECTRIC-OPTICAL PROPERTIES OF THE DIELECTRIC
LAYERS
A. Wafer Process Results
In order to allow the measurement of voltage breakdown,
leakage current, film stress, non-uniformity, refractive index
(RI) and dielectric constants single films of SiO2, Si3N4 and
TEOS were deposited at 150nm and 2000nm thickness on a
200mm substrate. The results showed that the RI was of
expected values and that the non-uniformity was at levels that
could be used in a production environment as shown in Table
I. Additionally, the film stresses were all compressive; this is
an important result as it is desirable to have a compressive
stress to prevent the formation of cracks in any deposited film.
This may not be clear intuitively from the shape of the
substrate. It should be remembered that if a tensile stress is
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present the film will be more prone to crack. In addition,
compressively stressed silicon nitride films are generally
acknowledged to give the best barrier properties. These are
widely used in CMOS multi-level metal interconnect scheme
[18].
TABLE I
WAFER PROCESS RESULTS
Film Type
Thickness (µm)
Non Uniformity 1σ (%)
RI
Stress (MPa)
SiO2 0.1486 0.69 1.4644 -
SiO2 1.9740 0.57 1.4636 -140 Si3N4 0.1522 1.52 1.9973 -
Si3N4 1.9392 1.49 2.0056 -220
TEOS 0.170 0.6 1.4514 - TEOS 2.1321 0.64 1.4595 -140
B. Voltage Breakdown and Leakage Current
To measure voltage breakdown and leakage current of the
films 150nm of the SiO2, Si3N4 and TEOS were deposited on
200mm low resistivity [p-type, B-doped, 0.005-0.02 Ohm-cm]
silicon wafers. 1.5mm diameter aluminum dots were then
evaporated through a metal stencil mask to form a test
structure. The low resistivity silicon substrate formed the
lower electrode and the evaporated aluminum formed the
upper electrode. A Keithley 2400 SMU was used to supply the
test voltage [0-200V] and a Keithley 6485 PicoAmmeter was
used to measure leakage current. All measurements were
conducted at room temperature with the voltage sweeping
from 0V to 200V in 5V steps. The current was measured at
each voltage step. The leakage current is quoted at 2 MV/cm.
The expected leakage current and break down voltages of
SiO2, Si3N4 and TEOS are 2.0E-9 A/cm2 and 4-10 MV/cm
respectively[29]. The results are shown in Table II.
TABLE II
LEAKAGE CURRENT AND BREAKDOWN VOLTAGES
Film
Type
Leakage Current
A/cm2
Breakdown
Voltage MV/cm
Dielectric
Constant
SiO2 2.26 × 10-9 10 4.71
Si3N4 2.26 × 10-9 6 6.73
TEOS 2.26 × 10-9 10 4.59
C. Dielectric Constants
In order to measure the dielectric constant of the SiO2, Si3N4
and TEOS a thickness of 2000nm was deposited on 200mm
low resistivity electrode [p-type, B-doped, 0.005-0.02 Ohm-
cm] silicon wafers. 2mm diameter Al dots were evaporated
through metal stencil mask to form a similar test structure
used for the voltage breakdown and leakage current tests. A
Keithley 2400 source-measure unit [SMU] was used as a bias
voltage supply [-200 to +200 V] and a Keithley 590 CV
analyzer was used for capacitance measurement. As in the
leakage current and breakdown voltage tests, the low
resistivity Si substrate formed the lower electrode.
Software-automated capacitance versus voltage measurement
K value can be determined from accumulation capacitance
using (1).
(1)
Where is the relative permittivity, is the permittivity of
free space, d is the film thickness, C is the measured
capacitance and A is the area of the evaporated aluminum dot
that forms the upper electrode. The results are shown in Table
II.
D. Combined Stress of the stacked Dielectric Layers
The combined stress (Sc) of the stacked dielectric layers
used in the optical stack can be determined by using (2),
)321(
)33()22(11
LTLTLT
LSLTLTLTLSLTSc
(2)
Where LT1 is the layer thickness of layer 1 and LS1 is the
layer stress of layer 1, and so on for layer 2 and 3. The layer
target thickness will be 2μm then,
MPaSc
Sc
166
)222(
)1402()2202(1402
As mentioned earlier it is desirable to have a compressive (-)
stress to prevent the formation of cracks in the deposited films.
Also if a tensile stress is present the film will be more prone to
crack. The level of stress also determines the thickness of
films that can be fabricated. The combined stress of layers of
stack 1 and 2 was identical at -166 MPa this is due to the SiO2
and TEOS having matching stress values. Although these
stacks are made of different materials a similar level of stress
was achieved by varying the deposition conditions to
effectively tune the inherent film stress [30-32]. If the films of
the optical stack are too thin then it will be prone to
mechanical damage. If they are too thick it will crack and this
will also degrade the optical properties.
A compressive stress of -166MPa is considered a good level
and suggests that the multi stack film will survive the etching
of the via [33, 34].
IV. OPTICAL ANALYSIS
A. Bayes-Spectral-Entropy-Based measure of focus using a
Discrete Cosine Function
The performance of the optical stacks was quantified against a
known reference, in this case an optical cover slip that was
0.1mm in thickness. The microscope used to image the
optical stack comprised of an Axiovert 135 inverted
microscope fitted with a x10 objective lens and EXi blue
monochrome fluorescence microscopy camera that utilized
1392 x 1040 pixels at a 6.4µm x 6.4µm pixel size. The
transmission illumination was from a halogen lamp at the top
input port. The camera exposure time and gain were controlled
manually. There were three sets of pictures imaged through
Stack 1, Stack 2 and the cover slip. A set of 20 images of a
human hair were taken stepping though a variance of focus
and then saved to a standard PC.
The images were then processed using a Bayes-Spectral-
Entropy-Based measure of focus using a Discrete Cosine .Aε
d.Cε
0
r
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Function (DCT) this technique is used to evaluate the optical
performance of devices and optical films and lenses [35]. In
order to estimate the depth of focus, a small area at the same
coordinates for all the images in each set of approximately
200x200 pixels was selected in a Matlab routine. These sub
images were then transformed to their spectral representation
via a discrete cosine transform and a measure of the focus was
obtained. The assumption is that when a typical image is out
of focus its "measure" (amplitude) is less than when it is
focused, in terms of the Entropy Based optical quality
evaluation technique then the stacks have comparable or better
optical quality than a standard glass cover slip as shown in Fig
4. The image focus profiles for our stacks are comparable to
that of a glass cover slip.
Fig. 4. Focus Intensity Comparison between the optical stacks and a standard
glass slide
In addition we have the “best in focus” images of a human
hair of Stack 1 and a cover slip shown in Fig. 5
Fig. 5 Best in focus of a human hair. a) Stack 1 b) Glass Cover Slip
B. Reflectivity Measurement
The Spectroscopy hardware used to measure the reflectivity
consisted of a PC based Ocean Optics SpectraSuite®
spectroscopy software, an Ocean Optics USB2000+
Miniature Fiber Optic Spectrometer and an optical fiber
assembly terminated with a standard SMA connector. Light
from a halogen lamp was sampled using a 100mSec capture
time. Experimentally determined spectra were compared to
computational predictions using a transfer matrix approach
with layer thicknesses and wavelength dependent refractive
index values obtained from the wafer process results.
The simulation presented a reflectivity calculation from the
dielectric stack over the visible spectrum typically used
with confocal microscopy. The data from the Ocean Optics
SpectraSuite® was then plotted against this predicted
module as shown in Fig. 6.
Fig. 6. (a) Stack 2: experimental v simulation (b) Stack 1: experimental v
simulation
It can be seen that there is reasonable general agreement
between the experimental and simulated data. The differences
seen between simulated and actual results in the 400-525nm
range are due to the low levels of light intensity produced by
the halogen lamp at this frequency range as shown in Fig 7.
The spectrometer used was an Ocean Optics USB2000+
Miniature Fiber Optic Spectrometer that digitizes the response
of the CCD detector to incoming photons. Due to the
0.55
0.6
0.65
0.7
0.75
0.8
0.85
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Inte
nsit
y
Focus Position
Dielectric Stack_1
Dielectric Stack_2
Cover slip
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limitation of acquisition system the low intensity at the 0-
525nm range caused poor signal to noise ratio within the
spectrometer.
Fig.7. The frequency spectrum of halogen lamp used in the reflectivity
measurement
The films that were deposited to measure the refractive indices
are single films and therefore the exact values of indices of the
individual layers within the stack cannot be measured
accurately. Similarly, the part of the substrate that was cleaved
in order to perform the SEM thickness measurements was in a
different area of the substrate used to perform the reflectivity
measurements and consequently the films non uniformity
could cause thickness variations.
Therefore an optimization algorithm was employed [36], to
iteratively refine film thicknesses to ensure an optimum fit
between measured and simulated intensities, and . The film thicknesses for the located minima
(i.e.
, where the tolerance ).
In both experiments is optimally matched to .
C. Testing the Optical Structure using Biological Cell lines
Optical stack 2 was tested for use within optical microscopy
by growing adherent lung epithelial cells (BEAS-2B) on the
surface of layer 3 (Si3N4), refer to fig 8 (a).
(a)
(b)
Fig. 8.(a) The optical stack tested using confocal microscopy. (b) LSM-710 laser scanning confocal microscope.
The lung cells were fluorescently labeled in specific spatial
locations with three fluorochromes of differing wavelength,
covering the visible spectrum (blue to red) and then imaged
with laser scanning confocal microscopy.
The substrate was first washed in 70/30 ethanol/H2O, and then
left soaking in this solution for a period of sixteen hours to
sterilize the growth surface prior to the addition of cells. This
is of particular interest from the materials standpoint as it not
only tested the physical strength of the optical stack but also
tested its moisture barrier properties. The substrate was then
washed three times with phosphate buffered saline (PBS) to
remove all traces of the alcohol and then placed in a Petri dish
containing 100% foetal bovine serum for 1 hour under aseptic
conditions.
The substrate was then transferred to a fresh Petri dish and
incubated at 37 °C, 5% CO2 for 12 hours with the BEAS-2B
cells to permit attachment. Cells were seeded at a
concentration of 4000 cells/cm2 in medium consisting of
Dulbecco’s Modified Eagle’s Medium (DMEM, D5796,
500mL available from Sigma Aldrich), supplemented with
10% foetal bovine serum, 1% Penicillin and Streptomycin. A
4nM concentration of quantum dot (QD) solution was
prepared by adding 4µl of 705nm emitting carboxylated
CdTe/ZnS quantum dot solution (Q21361MP, 250 µl @ 8µM,
Invitrogen), to 2 ml of the culture medium, and vortexed for 1
minute.
The existing cell medium covering the substrate was removed
and was replaced with this new QD loaded medium and
returned to the incubator for one hour to allow the quantum
dots to attach to the cells. The sample was then removed from
the incubator, the medium removed and the cells washed twice
with 4ml of PBS, to remove any stray, non-attached quantum
dots. The cells were then incubated at 37 °C, 5% CO2 in 2ml
of FACS FIX (1:10 BD Cell Fix:dH2O); enough to cover the
substrate. The FACS FIX was then removed and replaced with
4ml of PBS and placed in the fridge at 4 °C prior to
imaging. The sample was then washed with three changes of
Hank’s Buffered Salt Solution (HBSS, H6648, 500mL
available from Sigma Aldrich) prior to further fluorescent
labeling. The cell membranes were labeled with a wheat germ
agglutinin 555 Alexa Fluor® conjugate (WGA, W32464,
available from Life Technologies) at 5μg/mL in HBSS for 10
min in the dark. Cells were then covered with 10μL
0
0.2
0.4
0.6
0.8
1
1.2
300 500 700
No
rmal
ized
Inte
nsi
ty
Wavelength (nm)
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glycerol/TRIS buffered mountant supplemented with 1μg/mL
Hoescht 33342 nuclear stain (H3570, available from Life
Technologies) and a coverslip was placed over the optical
stack.
Confocal microscopy was conducted from underneath through
the optical stack using a LSM-710 laser scanning confocal
microscope using a 20x and 40x Plan-Neofluor objectives and
ZEN software version 2009 (Carl-Zeiss) as shown in Fig 8 (b).
Fig. 9. shows images of the cells obtained with 20x and 40x
objectives.
(a)
(b) Fig. 9. Three color fluorescence micrographs of BEAS-2B cells labeled with Hoechst 33348 (blue; nucleus) WGA-555 (green; cell membrane) and q-
tracker 705nm (red; endosomes). Fluorescence image obtained with (a) 20x
objective, (b) 40x objective,
The optical quality of the dielectric stack and the access
geometry of the wafer via are such that excellent light
collection is obtained allowing high resolution imaging of the
cells with clear delineation of the nanoparticle loaded vesicles
(red channel), cell nucleus (blue channel) and membrane
structures (green channel).
V. CONCLUSIONS
There were several design constraints in the fabrication of this
structure. Firstly, the optical via etched through the substrate
needed to be large enough to accommodate a microscope
objective lens and possess vertical side walls to allow multiple
vias to be fabricated closely together. The required vertical
anisotropic etch was achieved by using the Bosch process
employing advanced DRIE techniques. Given such a large via
this also required the optical stack to possess the physical
properties to survive the etch process, traverse the whole of
the silicon wafer and physically remain intact to support the
analysis of biological cell lines. The dielectric layers within
the stack were enabled to be of the required strength by
depositing sufficiently thick layers at the desired levels of
compressive stress. This was accomplished by utilizing mixed
frequency and general process control techniques during the
PECVD deposition process. Conversely, the thickness of the
stack also needed to be kept as thin as possible to prevent
adverse optical attenuation. Consequently a layer thickness of
2μm was seen as compromise between physical strength and
optical performance. Efforts to improve the optical properties
by further reducing the differences between the refractive
indices of the dielectric layers were not attempted as any
further changes to the refractive index would have degraded
the film electrical characteristics. This holds especially true for
the Si3N4 as any reduction in refractive index would also
reduce its moisture barrier properties. However, attempting to
improve the refractive index matching whilst maintaining
good electrical properties does give the opportunity for a
separate program of work.
We have successfully fabricated an optical stack using
materials that are considered standard in the semiconductor
industry and incorporating design rules that are commonly
used in the fabrication of 0.35µm node CMOS devices. The
structure has the optical characteristics to enable excitation
light to pass through without any serious attenuation that could
prevent the microscope objective allowing analysis of the
biological specimen. This is clearly demonstrated by the
clarity of the images of the BEAS-2B cells produced by
scanning confocal microscopy techniques shown in Fig. 9.
Furthermore, it is hoped that by using the predictive MatLab
model the RI and dielectric layer thicknesses of standard
CMOS architectures could be modified to accommodate
specific wavelength particular to unique biotechnology
analytical techniques[37].
Utilizing the optical performance of what would be considered
standard dielectric layers that also have good electrical
performance is a novel approach to LoC applications.
Benefits of this design methodology include significantly
reducing the cost of LoC fabrication techniques and enabling
the adaptation of a LoC devices to different applications. This
clearly makes a large advancement on the current state-of-the-
art possible where silicon ICs have been adopted for biologic
applications including cell sorting but suffer from the
requirement that after sorting cells are removed from the chip
for detailed analysis preventing full in-situ experimentation
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This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI10.1109/JSEN.2014.2367238, IEEE Sensors Journal
8
and exposing the cells to possible damage or contamination.
This platform will allow single cells or other particles of
interest to be positioned over the optical windows after sorting
‘on-chip’ and studied by biologists ‘in-situ’ on their most
favored analytical tools such as standard inverted microscope
platforms. The use of the CMOS architecture also allows
interesting possibilities to add further sensing functions in
tandem on the chip (resistance, capacitance, magnetic and
optical) to expand the biological insights gained from
analysis of the sample.
This research is ongoing and funded by the Engineering and
Physical Science Research Council (EPSRC) First grant
scheme; grant number EP/I038799/1.
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